Bidding to win 20 for the first time during a career that started in 1991, the 39-year-old Mussina again struggled against his former team. The right-hander gave up four runs and nine hits over six innings and left with Baltimore ahead 4-3.
Mussina is 0-2 with an 8.49 ERA in three starts against the Orioles this season. He has allowed three home runs in his last 11 starts - all of them to Baltimore, and two to Ramon Hernandez.
Abreu led off the eighth with his fourth hit, a single off Jamie Walker (1-1). Alex Rodriguez followed with a double, sending Abreu to third, and Jason Giambi popped out. Rookie Kam Mickolio replaced Walker and immediately threw a wild pitch to score Abreu, and Nady followed with an opposite-field single to right to make it 5-4.
Cody Ransom hit a three-homer in the ninth off Fernando Cabrera and Nady followed with a solo shot. Earlier, Robinson Cano and Jose Molina hit successive home runs.
Jose Veras (4-2) worked the seventh, Damaso Marte got two outs in the eighth and Mariano Rivera finished for his 29th save in 30 tries.
Abreu's five hits matched a career high, set Aug. 8, 1999, with Philadelphia against Arizona.
Derek Jeter got his 2,500th career hit, a bloop single in the first inning. He joins Lou Gehrig and Babe Ruth as the only players to have 2,500 hits as Yankees.
Hernandez homered and drove in two runs, and Aubrey Huff also had two RBIs for the Orioles.
Baltimore took a 4-3 lead in the sixth. Kevin Millar hit a one-out double, advanced on a single by Luke Scott and scored on a fly to the warning track by Hernandez.
But it wasn't enough to beat Mussina, whose only loss since June 30 was against the Orioles.
Recalled from Triple-A Norfolk before the game, Baltimore starter Radhames Liz yielded hits to the first three New York batters. Johnny Damon doubled, took third on Jeter's milestone hit and scored on a single by Abreu.
Baltimore tied it in the bottom half on a two-out RBI single by Huff.
Huff gave the Orioles a 2-1 lead in the third, bouncing an RBI single between the legs of second base umpire Ed Rapuano after Nick Markakis and Melvin Mora singled with one out.
Hernandez made it 3-1 in the fourth with his second home run in two games and 14th of the season. The drive also extended his hitting streak to 12 games, one short of his career high.
Cano and Molina homered in the fifth to tie it at 3.
