Billy Reid's team have now endured a horrific start to the season with eight goals conceded and none scored and were outplayed by Hearts in an SPL game that saw both teams reduced to 10 men on Saturday.
Hearts were two ahead by half-time with fine strikes by Calum Elliot and David Templeton, and a depleted Hamilton, missing several senior players, could not respond after the interval.
Ruben Palazuelos was ordered off for Hearts for two yellow card offences, but that was evened out when Martin Canning was red-carded for a foul on Lee Wallace that set up Kevin Kyle to score a Hearts third from the penalty spot.
Hamilton's misery was compounded with nine minutes remaining as Elliot was allowed to run through far too easily and make it a 4-0 reverse for the second week running.
Ismael Bouzid was restored to the Hearts defence after suspension as the Edinburgh club made their first trip to Hamilton since a controversial meeting last December.
Five players and the Hearts masseur, Alan Robson, were sent off during and after that match following an ugly tunnel fracas that later saw both clubs fined.
Bouzid replaced Jason Thomson for Hearts, while Hamilton made two changes from their heavy 4-0 loss to Aberdeen on the Premier League's opening day.
Joel Thomas, recently returned to the club from Colchester, and Brian McQueen were drafted in for David Buchanan and Gary McDonald. Alex Neil and Mark McLaughlin were among their sidelined senior players.
Thomas was keen to make an impression, but overdid it slightly in the fourth minute flying into a tackle on Bouzid that resulted in the game's first booking.
In the sixth minute, Hearts took an early lead with a finely crafted strike, Suso Santana playing in Elliot from the right flank who then curled in a brilliant effort beyond Tomas Cerny in the Hamilton goal.
Palazuelos collected a needless booking for Hearts for kicking the ball away as Hamilton sought a quick response to going behind.
Hamilton went two behind after 24 minutes and only had themselves to blame after a wayward backpass from Simon Mensing saw an attempting diving header from goalkeeper Cerny.
With Hamilton unable to properly clear, Palazuelos collected the ball and fed Templeton who produced a powerful angled drive for 2-0.
After 29 minutes, Craig Thomson had no complaints at being booked after a dangerously late tackle on Hamilton's Dougie Imrie.
Elliot threatened again for Hearts three minutes before the interval as he looked to have got in behind the Hamilton defence, only for Canning to rescue the situation with a timely block.
Hamilton made a change at half-time, withdrawing Jack Ross, the right-back, for the more attack-minded Jim McAlister as they set about an unlikely comeback.
The home team had a penalty claim rejected three minutes after the restart when Lee Wallace looked to have impeded Flavio Paixao inside the penalty area.
Ironically, Hearts quickly broke upfield with Wallace and he had a spot-kick claim of his own refused when he fell under challenge from the substitute McAlister.
Hamilton were looking brighter and might have pulled a goal back after 49 minutes when Imrie's cross from the left was met with a powerful close-range header from Flavio Paixao that crashed against the crossbar.
Cerny failed to deal with a Thomson corner on 55 minutes and Suso Santana should have done much better with a clear shooting chance than to blaze the ball over the bar.
Hearts were reduced to 10 men in the 63rd minute when Palazuelos paid for his earlier silly booking with a second caution that was beyond dispute, an ugly studs-up foul on Flavio Paixao.
Hearts manager Jim Jefferies at once took off Templeton to introduce Adrian Mrowiec, while Hamilton introduced McDonald for the ineffectual McQueen.
Hearts brought on Kevin Kyle for Santana and he almost made an immediate impact, looping a header from Thomson's cross over the head of Cerny only for it to bounce narrowly wide.
Hamilton's fate was sealed in the 75th minute when Canning, having given the ball away, was punished for a trip on Wallace as he surged into the area, meaning the double punishment of a red card and a penalty.
Kyle volunteered and thumped the ball into the top right corner.
Worse was to come for Hamilton on 81 minutes when Kyle Wilkie lost the ball and Elliot got a clear run at goal before claiming his second of the game with a composed low finish.
Elliot was denied a hat-trick in the closing minutes when his shot was tipped over by Cerny, but by then the damage had been done for Hamilton.