The LA Galaxy attacker was in fine form for Jurgen Klinsmann's men as he dealt opposition manager Craig Levein his side's heaviest defeat since taking charge of his country
Michael Bradley and Jermaine Jones were also on the scoresheet, with Geoff Cameron’s first-half own goal failing to offer any parity.
Manager Craig Levein set up with an attacking lineup including debutant Matt Phillips, with Shaun Maloney also included and Kenny Miller leading the line. There was also a place for Barry Bannan, while Andy Webster made his first start since March 2010, Levein’s first game in charge.
For the USA, Donovan made his 139th appearance for his country whilst Maurice Edu of Rangers featured in midfield.
The hosts flew out the traps and were gifted the opener inside just three minutes. Following some poor defending from Phil Bardsley, Donovan shot high into the net after his previous effort being blocked by Allan McGregor.
This lead was doubled soon after. Jones passed to Bradley in space 30 yards out who hammered an unstoppable volley on 11 minutes.
Despite being on the receiving end for much of the opening exchanges, Scotland clawed their way back into the contest, Bardsley’s cross finding Miller at the back post and his header deflected home by Cameron.
The USA appeared undeterred by this, though, and were soon piling on the pressure once more, Jose Torres striking the bar with a free kick just before half-time.
After the break the game pattern failed to change as the visitors struggled to contain the hosts' attacking flair as Donovan hammered the post with another effort.
Levein made a host of changes, introducing Don Cowie, Russell Martin and Steven Whittaker, but it was soon after these substitutions that they conceded once again.
Jones created the opportunity, playing in Donovan, who calmly slotted past McGregor.
Just five minutes later Donovan completed his hat-trick, his effort going in off the post and just out of the reach of the despairing Scottish keeper.
The scoring was completed with 20 minutes to go, the hat-trick hero delivering a cross into the area which Jones headed powerfully home to seal an impressive victory.