Saltalamacchia amassed four RBI with a three-run homer and a solo shot, and Ortiz put the Red Sox ahead 4-0 with his round-tripper in the third inning.
Mike Carp also went deep for the American League East-leading Red Sox.
Ryan Dempster (4-6) logged the victory, allowing three runs on six hits over six innings. The veteran right-hander walked two and struck out six.
Angels starter Joe Blanton (1-10) was torched for seven runs (six earned) on eight hits in five innings.