Felix, who eased to victory in the 200M on Friday, became the first athlete to win double maximum points in a Diamond League meeting and is considering running both events at next year's world championships and the 2012 London Olympics.
"I really hope so," Felix said when asked about doing the double in a trackside interview "I'm going to work really hard and we'll see." But the American found the going tough over the longer event in front of a packed Crystal Palace on a breezy, overcast day.
After going off quickly, she came under pressure from Russia's European champion Tatyana Firova and world indoor gold medallist Debbie Dunn in the home straight.
However, the triple world 200 metres champion held her form to win in 50.79 seconds. Firova was second in 50.84 and Dunn third 0.05 behind.
"It was a tight race and I really had to rely on my endurance," said Felix who also won the 400 at the Doha and Eugene Diamond League races.
Felix's compatriot Christian Cantwell had a less happy time at Crystal Palace when the world shot put champion suffered his first defeat in 21 meetings.
Cantwell struggled from the start, opening with a no-throw, but pulled off 20.78 on his final attempt for third behind fellow American Reese Hoffa, who threw 21.44 and Poland's Tomasz Majewski on 21.20.
There was also a surprise defeat for Carmelita Jeter in the women's 100 metres final when she finished second to fellow American Marshevet Myers in a tight race.
Myers, who clocked 10.99 in her heat, held off the favourite to win in 11.01 for her first Diamond League victory. Jeter was second in 11.06.
American David Oliver maintained his unbeaten record outdoors this year with a convincing win in the 110M hurdles. The 28-year-old led from the first barrier and equalled Briton Colin Jackson's meeting record of 13.06.
Wallace Spearmon, who was seventh behind Tyson Gay in Friday's 100M metres final, was back on more familiar ground when he won the 200M. The American world championship bronze medallist ran a good bend and powered away in the final 40 metres for a clear victory in 20.12.
His compatriot Jeremy Wariner notched his fifth Diamond League victory over 400M holding off fast-finishing Jamaican Jermaine Gonzales, the quickest man in the world this year, to win in 44.67.
Results: Men: 200M: Wallace Spearmon (US) 20.12 seconds, 1; Churandy Martina (Ned Antilles) 20.42, 2; Jaysuma Saidy Ndure (Nor) 20.43, 3.
400M: Jeremy Wariner (US) 44.67, 1; Jermaine Gonzales (Jam) 44.80, 2; Ricardo Chambers (Jam) 45.18, 3.
1600M: Augustine Choge (Ken) 3:50.14, 1; Mekonnen Gebremedhin (Ethi) 3:50.35, 2; Leonel Manzano (US) 3:50.64, 3.
110M hurdles: David Oliver (US) 13.06, 1; Dwight Thomas (Jam) 13.32, 2; Garfield Darien (Fra) 13.34, 3.
High jump: Ivan Ukhov (Rus) 2.29 metres, 1; Jesse Williams (US) 2.27, 2; Donald Thomas (Bah) 2.27, 3.
Long jump: Dwight Phillips (US) 8.18, 1; Morten Jensen (Den) 7.96, 2; Chris Tomlinson (Bri) 7.92, 3.
Shot put: Reese Hoffa (US) 21.44, 1; Tomasz Majewski (Pol) 21.20, 2; Christian Cantwell (US) 20.78, 3.
Discus throw: Gerd Kanter (Est) 67.82, 1; Zoltan Koevago (Hun) 65.54, 2; Virgilijus Alekna (Lit) 65.33, 3.
Javelin throw: Andreas Thorkildsen (Nor) 87.38, 1; Matthias De Zordo (Ger) 86.97, 2; Tero Pitkamaki (Fin) 84.71, 3.
Women: 100M: Marshevet Myers (US) 11.01 seconds, 1; Carmelita Jeter (US) 11.06, 2; Blessing Okagbare (Nig) 11.10, 3.
400M: Allyson Felix (US) 50.79, 1; Tatyana Firova (Rus) 50.84, 2; Debbie Dunn (US) 50.89, 3.
800M: Mariya Savinova (Rus) 1:58.64, 1; Janeth Jepkosgei (Ken) 1:59.16, 2; Jemma Simpson (Bri) 1:59.26, 3.
400M hurdles: Kaliese Spencer (Jam) 53.78, 1; Zuzana Hejnova (Cze) 55.11, 2; Eilidh Child (Bri) 55.16, 3.
3000M steeplechase: Milcah Chemos Cheywa (Ken) 9:22.49, 1; Yuliya Zarudneva (Rus) 9:22.60, 2; Lydia Jebet Rotich (Ken) 9:23.68, 3.
Triple jump: Yargelis Savigne (Cub) 14.86 metres, 1; Olga Rypakova (Kaz) 14.74, 2; Olha Saladuha (Ukr) 14.40, 3.