Byrd and Davis connected on consecutive pitches from Ian Kennedy in the third inning. Murphy hit a two-run shot an inning later to give the Mets a 5-1 lead.
Niese (5-6) allowed one run on six hits in six innings in his second start since returning from the disabled list. Niese struck out a season-high nine and walked one with one hit batter. Niese and three relievers combined to strike out 13, running New York's two-game total to 28.
Byrd has driven in six runs in his last three games after going without an RBI for the previous 13 games. Before he homered, Murphy had just one extra base hit in his last 20 games.
Davis has four homers off Kennedy (4-9) in only nine at-bats.
San Diego has dropped eight of 10 and fell into last place in the NL West with the Giants' win over Miami.
Byrd led off the third inning with his 19th home run and, on the next pitch, Davis hit homer No. 7. It was only the second time this season that New York has hit consecutive home runs.
Kennedy, acquired in a trade from Arizona on July 31, allowed five runs on seven hits over 4 2-3 innings in his third start for San Diego. The righty, who has allowed 22 home runs, struck out seven and walked four.
Will Venable ran his career-high hitting streak to 13 games with a solo homer in the third. Venable's 16th home run extended his career high.
Yonder Alonso added an RBI single in the eighth and Jedd Gyorko had three hits for San Diego, including a double. Gyorko has nine hits in his last six games, six for extra bases.
NOTES: Kennedy lost for the first time (4-1) against the Mets in six career starts . Padres LF Carlos Quentin is expected to miss another seven to 10 days with a strained right knee. Quentin received a second opinion from the Kerlan-Jobe Orthopaedic Clinic in Los Angeles on Thursday and San Diego manager Bud Black said the result was "the same findings that our team doctors had." . Slumping New York rookie CF Juan Lagares was held out of the starting lineup. Lagares is hitting .210 (13 for 62) in August and is hitless in his last 13 at-bats with five strikeouts . The teams continue their four-game series Saturday night with Mets RHP Jenrry Mejia (1-2, 2.22 ERA) set to face Padres RHP Edinson Volquez (8-10, 5.80).