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Federalism involves a great deal of power sharing, both at administrative and governmental levels. Federalism accepts the concept called 'right to self determination' to varying degrees, including 'the right to secession'. The right to secession has long created doubt in the minds of many that federalism leads to separatism.
Is there significant evidence to substantiate the proposition that federalism inevitably leads to the separation of single states?
There's no easy answer here because each Federal government system is different. Let's contrast the EU with the United States (both are Federal systems in a general sense)
More concisely, how nationalistic are the people for the Federal system? The United States has a pretty decent cohesion overall. Few people were cheering when the September 11 attacks happened. By contrast, the European Union is trying to unify multiple separate countries, each with its own people, economy, and, in many cases, language.
The first official languages of each of the 28 Member Countries has the status of an official language of the European Union. In total there are 24, with Irish, Bulgarian and Romanian gaining official language status on 1 January 2007, when the last two countries joined the European Union, and Croatian becoming official in 2013.
It's also worth noting that some countries in the EU (notably Germany) hold more power (respectively), thanks to their GDP and population size.
The EU doesn't have absolute power over its members, unlike the US where Federal laws trump state laws. Wikipedia describes EU state sovereignty like this
While the member states are sovereign, the union partially follows a supranational system that is comparable to federalism. Previously limited to European Community matters, the practice, known as the "community method", is currently used in most areas of policy. Combined sovereignty is delegated by each member to the institutions in return for representation within those institutions. This practice is often referred to as "pooling of sovereignty".[38] Those institutions are then empowered to make laws and execute them at a European level.
Because each state is its own country, secession is a very real threat to the EU (see brexit for a prime example).
Most US states, however, lack their own country-level mechanisms (Federal Reserve, military, diplomatic channels, etc). These present a serious barrier to secession. Additionally, the US Constitution has no provisions for secession, unlike the EU, and numerous legal rulings against it would make it very difficult (not counting the US civil war, which was fought over the issue).
The US shares a single economy. The EU mostly shares an economy, but some members (i.e. the UK) opted to keep their own currency. But the real problem the EU has faced is that some countries abused the economic union
The 2001 introduction of the euro reduced trade costs among Eurozone countries, increasing overall trade volume. Labour costs increased more (from a lower base) in peripheral countries such as Greece relative to core countries such as Germany, eroding Greece's competitive edge. As a result, Greece's current account (trade) deficit rose significantly.
As the Great Recession spread to Europe, the amount funds lent from the European core countries (e.g. Germany) to the peripheral countries such as Greece began to decline. Reports in 2009 of Greek fiscal mismanagement and deception increased borrowing costs; the combination meant Greece could no longer borrow to finance its trade and budget deficits at an affordable cost.
A country facing a “sudden stop” in private investment and a high (local currency) debt load typically allows its currency to depreciate to encourage investment and to pay back the debt in cheaper currency. This was not possible while Greece remained on the Euro.[14] Instead, to become more competitive, Greek wages fell nearly 20% from mid-2010 to 2014, a form of deflation. This significantly reduced income and GDP, resulting in a severe recession, decline in tax receipts and a significant rise in the debt-to-GDP ratio. Unemployment reached nearly 25%, from below 10% in 2003. Significant government spending cuts helped the Greek government return to a primary budget surplus by 2014 (collecting more revenue than it paid out, excluding interest)
This crisis lead to a lack of confidence in the Euro, and the economic union as a whole (with some calling for Greece to be expelled from the Euro) and likely helped play a role in Brexit
I can think of several nations that did not have the right to secession that led to separate states. For example, the Soviet Union. Or the former Yugoslavia. Or what is now the United States when it was part of the United Kingdom. Claiming that there wasn't a right to secession still ended up with separation.
And of course there are any number of states with separatist movements that do not allow secession. In some cases, this has led to terrorism, atrocities, or oppression.
It is possible that a right to secession eases these tensions. At least they tend to discharge without violent conflict. I'm not sure that we have enough examples to tell if having an explicit right to secession makes separation more or less likely.
Generally, a Federation is a group of States (Provinces, Districts, Cantons, etc) that cede certain powers to the Federal State that will make a collective decision for all states regarding that issue. In a National Federation, this is typically collective foreign authorities and military authorities, and the Federation Level government is collectively making a decision in the matters of power for the individual member state. Thus, when Federal Law is made on an issue it has authority over, it is the law for all member states by default. However, the Federal State cannot make laws for the Member State that the Member State has authority over (hence why certain states in the U.S. have sales tax and others do not.).
Confederations are a similar animal but with an important distinction. Under a confederation, all member states are fully sovereign with the Confederation State acting as a mediator of collective treaties between the member states. When a Confederation creates a new "law" the law must be adopted at the state level to have effect in a particular member state (it's not automatic law for all member states like it would be in a Federation). As a general rule, the prime difference between a Federation and a Confederation is that the Confederation grants at the very least de facto right of secession to its member states (if not explicitly spelling out the procedure), where a Federation does not. During the waning days of the U.S. Civil War, at least one Confederate State was threatening to secede from the confederacy outright and many of the organizational problems of the CSA were a result from the deliberate weakening of the centralized power.
Another comparison between a Federation and Confederation is the scope of the National level government laws on the individual. Federal government may make laws that govern the individuals of any member state so long as they are laws that fall into the Federal Government's wheel house. Confederations do not typically make laws regarding an individual, but rather, laws that affect only the interrelation of the state. Again, if the member state does not like a particular Confederate State level law, it can enter into procedures to leave the Confederation.
Confederations typically do not last long before either breaking apart or devolving/evolving into a Federation. Typically, they form to make quick co-operative governments during transitional periods while more nuanced rules for government are worked out (classically seen with the United States, which was a confederation under the Articles of Confederation before becoming a Federation under the Constitution of the United States. In fact, the key differences between the Articles and the Constitution are additional empowerment of the National government to address problems that arose by the weaker Confederation government having not been given those powers by the state.)
TL;DR: Federation Member States have limited Sovereignty and ceded certain powers to a Federation upon entering it. Upon entry, they are bound by the Federation's decision on all matters related to the ceded powers and do not have a right to succeed from the Federation. Confederations Member States are fully sovereign and set up the Confederation Government to be an mediator between all member states. Confederation government decisions are not binding and must be agreed upon by member states before they become effective law. Because of this, a member state does have de facto right to secession, which may or may not be codified by Confederation legal documents.
