Their punitive expedition against Eretreia and Athens losing the battle of Marathon to the Athenian and Plataean armies.
The battle of Marathon 490 BCE.
1942
The First major battle was Bull Run, where an expected Union victory was turned into a defeat
Defeat of the German/Nazi forces in WW2.
Al Leiter was the first pitcher to defeat all 30 Major League teams.
Bull Run.
First Bull Run
I don't know about major, but the first naval battle in the historical record was Hittites defeat Cypriots near Cyprus
The first major win was the Battle of Saratoga.
The major battle was with the Persians for Kandahar-The Mughal-Safavid War.
He first established firm control over the Greek city-states to protect his home base of Macedonia, and be a source of manpower. He then set about capturing the Mediterranean eastern seaboard to remove the threat of Persian naval invasion of Greece and Macedonia. He then defeated the Persians in two major battles - Issus and Gaugamela, breaking their unified power. With coordinated opposition broken, he then defeated the remaining Persian eastern provinces one by one.
First Manassas(Bull Run) July 21, 1861.