Hamsik produced a superb performance to inspire Slovakia. The Napoli star scored one and set up the other for Weiss at Stade Pierre-Mauroy in Lille, to give his country their maiden European Championship victory after a 2-1 loss to Wales in their Group B opener.
Hamsik found the net with a stunning strike on the stroke of half-time to give Slovakia a 2-0 lead, 23 minutes after playing provider for Weiss.
Weiss took advantage of an outstanding long ball from Hamsik, beating a pair of Russia defenders and thumping Slovakia into the lead.
Denis Glushakov got one back for Russia 10 minutes from time with a well-placed header, but they were unable to complete the comeback despite a heavy spell of late pressure.
Jan Kozak's Slovakia will now look to make sure of their place in the last 16 against England while Russia's progression hangs in the balance ahead of the group-stage finale with Wales, after a 1-1 draw with the Three Lions earlier in the tournament.
Both sides looked fired up in the early stages of this Group B tie in Lille, going hard into challenges and belting a couple of powerful shots from distance - Hamsik going closest with his left foot.
Weiss was causing plenty of problems with his mazy dribbling as Slovakia applied most of the pressure in the first half.
Russia looked very dangerous on the counter attack, and came extremely close to breaking the deadlock through Fedor Smolov in the 28th minute.
Artem Dzyuba, making the most of his size to win physical battles, found Smolov who had the time and space to send a low drive from outside the box just centimetres wide of the post.
However, it was Slovakia's pressure and Weiss' wonderful skill that paid off to open the scoring just after the half hour mark. Hamsik found Weiss with a great lobbed pass, who then cut inside, ditching two defenders in the process, and drove a powerful finish past helpless Russian keeper Igor Akinfeev.
Weiss and Hamsik teamed up again to extend Slovakia's lead right before half time.
Weiss the provider this time as he caught Russia unawares with a quickly taken corner - a simple short pass along the ground to Hamsik who dummied with his left to pass one defender then sent a snapshot in off the far post from a tight angle.
The second half initially didn't show any signs of improvement from Russia, as Smolov's shot back in the 28th minute remained their most recent.
Russia's midfield substitutes failed to add urgency and going into the 70th minute Slovakia still had concerning amounts of freedom going forward.
The game changed suddenly when the Russians pulled a goal back in the 80th minute - Glushakov heading home from Shatov's cutback.
The remaining 13 or so minutes of play were frantic as finally Slutsky's men poured forward with urgency, but it was too little too late for them as Slovakia recorded a 2-1 win to seal their first points of the tournament.
Key Opta Facts:
- Slovakia became the first team to score twice in the first half at this tournament, scoring both of their shots on target in the opening period.
- Russia have failed to keep a clean sheet in their last seven European Championship fixtures.
- Vladimir Weiss’ opener ended Slovakia's run of 275 minutes without scoring against Russia.
- Russia have failed to win any of their last 10 games at the Euros in which they’ve conceded the opening goal (D2 L8).
- Four of Russia's last five goals at the Euros have been in the 79th minute or later.