The 21-year-old will move to St Mary's for an undisclosed fee having agreed a five-year deal to keep him at the Club until the summer of 2017.
Mayuka underwent a successful medical earlier today and will be allocated the number 24 shirt once his move is complete.
The Zambia international has already been granted a work permit by the Home Office and Saints are now awaiting entry clearance for the deal to be fully ratified, which is expected to happen before the end of this week.
Should the formalities be resolved as anticipated, Mayuka will link up with his new team ahead of Sunday's Barclays Premier League home fixture against Manchester United.
"Emmanuel is a lightning-quick striker who I am sure will excite the fans," First Team Manager Nigel Adkins said of the Club's fifth summer signing.
"He is only 21 years old but already has a great deal of experience, notably so at international level.
"He will bring something different to the group that we already have here at Southampton, and I look forward to seeing him pull on our shirt for the first time."
In Profile: Emmanuel Mayuka
Mayuka has a reputation as one of the brightest talents to come out of Africa in recent years, having moved to Europe in 2008 when he joined Maccabi Tel Aviv from his first club Kabwe Warriors.
He scored seven goals in 29 games for the Israeli outfit, leading him to sign a five-year deal with Young Boys in May 2010.
Mayuka recorded an impressive goalscoring ratio in his 84 appearances for his Bern-based former club, finding the back of the net 32 times in two seasons.
It is on the international stage, though, that the five-foot-nine frontman has made his greatest achievements.
Despite his relatively young age, Mayuka has already been capped 36 times by Zambia since making his debut in 2007.
Three of his ten international goals came in his country's successful 2012 Africa Cup of Nations campaign – he netted against Senegal, Libya and Ghana as the Chipolopolo won the tournament for the first time in their history.
He finished the competition as joint-top goalscorer as one of seven players to score three times, but was awarded the Golden Boot by virtue of having an extra assist to his name.