The new ad, called Hands, will air on television from Feb 12. It continues the Good Things Come To Those Who Wait theme recently revived for the brand, and features a pair of stop-frame animated hands doing a quirky dance.
Russell Jones, marketing director for Guinness at Diageo GB, said: "We wanted to surprise people and do something a little bit different and quirky, so it's not one of those blockbuster ads that costs millions of pounds to make.
"It started from the ad agency as an idea for something that might work online but we've decided it could really get into the minds of consumers on a bigger scale."
The ad will appear on TV during "key waiting moments", such as half-time in sports fixtures or immediately before the start of a major TV series.
The campaign also includes online advertising as well as digital outdoor advertising in stadiums, pubs and key London Underground stations.
A website will give consumers the chance to make a customised version of the ad at www.guinnesshands.com. The site also contains behind-the-scenes footage and information on the making of the advertisement.
The campaign will run until the end of March and aims to support licensees and retailers during the spring period. Diageo is also running on-pack promotions to make the most of Six Nations.