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It restored some credibility to his reputation after serving a 21-month doping ban, then fighting a court battle against the International Olympic Committee before being allowed to run in the 2012 Olympics.
The 27-year-old, who won his previous title in 2009 a year after winning Olympic gold, posted the fastest time of the year of 43.74 seconds to take gold while compatriot Tony McQuay ran a personal best (44.40sec) for second place and Luquelin Santos of the Dominican Republic was third (44.52sec).
Olympic and defending champion Kirani James of Grenada appeared to tighten up in the finishing straight and faded to finish seventh of the eight-man field.
"It just didn't work out for me today," said the 20-year-old James, who beat Merritt for gold two years ago at Daegu, South Korea.
"It is back to the drawing board, see what's going on. I didn't come into the Worlds expecting this but you just move forward from this."
Merritt, who failed to make it past the heats in the Olympics pulling up injured, burst from the blocks and, by the time they rounded the final bend, it was all for James to do.
However, the spark that has seen him dominate the event for the past two years was not there and instead of producing his trademark burst down the straight he was swallowed up by the rest of the runners.
Merritt was never threatened but McQuay, 23, stormed through to take a deserved second place and Santos produced another excellent performance at the age of 19 to add a second minor medal from a major final to what promises to be an impressive collection.
Yousef Ahmed Masrahi never threatened to become only Saudi Arabia's second world championship medallist.
Having been impressive in his first round heat and the semi-final, the 25-year-old failed to cope with the pressures of both an expectant people back home and his first major global final as he finished sixth.
"This is a race that was top class and could have been won by anyone," he said.
"It was so strong a race that the Olympic champion did not win. For me it has been a really good experience and I will be stronger for it and come back better for the next championships in two years time."
For Merritt, though, it will not only mean $100 000 in first place prize money but also go some way towards rebuilding his standing which had not only seen him plunged into disgrace but also become a source of ridicule during the doping saga.
He tested positive for steroids three times in late 2009 and was banned before winning an appeal to an arbitrator and successfully fighting an Olympic rule that would have banned him from the London Games.
That victory at the Court of Arbitration for Sport came at the cost of an embarrassing revelation, with Merritt saying he'd tested positive because he took a $6 male enhancement product, ExtenZe, that contained the banned substance DHEA.
Fourth day finals results on Tuesday at the World Athletics Championships:
Men:
400 m:
1. LaShawn Merritt (USA) 43.74
2. Tony McQuay (USA) 44.40
3. Luguelin Santos (DOM) 44.52
4. Jonathan Borlee (BEL) 44.54
5. Pavel Maslak (CZE) 44.91
6. Yousef Ahmed Masrahi (KSA) 44.97
7. Kirani James (GRN) 44.99
8. Anderson Henriques (BRA) 45.03
800m:
1. Mohammed Aman (ETH) 1:43.31
2. Nick Symmonds (USA) 1:43.55
3. Ayanleh Souleiman (DJI) 1:43.76
4. Marcin Lewandowski (POL) 1:44.08
5. Andrew Osagie (GBR) 1:44.36
6. Duane Solomon (USA) 1:44.42
7. Pierre-Ambroise Bosse (FRA) 1:44.79
8. Abdulaziz Mohammed (KSA) 1:46.57
Discus:
1. Robert Harting (GER) 69.11
2. Piotr Malachowski (POL) 68.36
3. Gerd Kanter (EST) 65.19
4. Martin Wierig (GER) 65.02
5. Victor Hogan (RSA) 64.35
6. Robert Urbanek (POL) 64.32
7. Vikas Gowda (IND) 64.03
8. Victor Butenko (RUS) 63.38
9. Yennifer Frank Casaas (ESP) 62.89
10. Jorge Hernandez (CUB) 62.88
11. Julian Wruck (AUS) 62.40
12. Mario Pestano (ESP) 61.88
Women:
Pole vault:
1. Yelena Isinbayeva (RUS) 4.89
2. Jennifer Suhr (USA) 4.82
3. Yarisley Silva (CUB) 4.82
4. Silke Spiegelburg (GER) 4.75
5. Fabiana Murer (BRA) 4.65
5. Anastasia Savchenko (RUS) 4.65
7. Angelina Zhuk-Krasnova (RUS) 4.65
8. Jirina Ptacnikova-Svobodova (CZE) 4.55
8. Lisa Ryzih (GER) 4.55
10. Kristina Gadschiew (GER) 4.45
20km walk:
1. Elena Lashmanova (RUS) 1:27:08
2. Anisya Kirdyapkina (RUS) 1:27:11
3. Liu Hong (CHN) 1:28:10
4. Sun Huanhuan (CHN) 1:28:32
5. Elisa Rigaudo (ITA) 1:28:41
6. Beatriz Pascual (ESP) 1:29:00
7. Anezka Drahotov (CZE) 1:29:05
8. Ana Cabecinha (POR) 1:29:17
9. Julia Takacs (ESP) 1:29:25
10. Eleonora Giorgi (ITA) 1:30:01
3000m steeplechase:
1. Milcah Chemos Cheywa (KEN) 9:11.65
2. Lydia Chepkurui (KEN) 9:12.55
3. Sofia Assefa (ETH) 9:12.84
4. Hiwot Ayalew (ETH) 9:15.25
5. Etenesh Diro (ETH) 9:16.97
6. Hyvin Kiyeng Jepkemoi (KEN) 9:22.05
7. Valentyna Zhudina (UKR) 9:33.73
8. Antje Mldner-Schmidt (GER) 9:34.06
9. Gesa Felicitas Krause (GER) 9:37.11
10. Eilish McColgan (GBR) 9:37.33
Heptathlon:
2. Brianne Theisen (CAN) 6530
3. Dafne Schippers (NED) 6477
4. Claudia Rath (GER) 6462
5. Katarina Thompson (GBR) 6449
6. Sharon Day (USA) 6407
7. Eliska Klucinova (CZE) 6332
8. Antoinette Djimou (FRA) 6326
9. Karolina Tyminska (POL) 6270
10. Nadine Broersen (NED) 6224
