Match ends, Newcastle United 2, Southampton 2.
Southampton earned a point at Newcastle thanks to substitute Shane Long's late goal.
Graziano Pelle met Cedric Soares' long ball to head Saints into an early lead, before Papiss Cisse equalised by chesting in a deflected cross.
New £14.5m signing Georginio Wijnaldum then scored a powerful header on his Premier League debut to give Newcastle the lead early in the second half.
But Long struck 10 minutes from time, heading in a Dusan Tadic cross.
Southampton forward Sadio Mane had two chances to win the match in injury time. First he saw an effort blocked by Jack Colback, before another shot drifted inches wide of the post.
Saints manager Ronald Koeman followed the match from home as he recovered from an operation on his Achilles tendon, while brother and assistant manager Erwin gave a first Premier League start in 491 days to striker Jay Rodriguez.
England striker Rodriguez was making his first Premier League start in 16 months.
The 26-year-old ruptured his anterior cruciate knee ligament in April 2014, only making his competitive return in the Europa League qualifying match on Thursday.
His lack of match action showed and he was replaced by Long on 65 minutes after just one shot, which was off target.
Soares, the Portugal international signed for £3.6m from Sporting Lisbon, impressed on his debut, showing plenty of endeavour going forward and supplying a deep cross for Pelle's goal.
His replacement Cuco Martina became only the second player from the Caribbean nation of Curacao to play in the Premier League after West Brom's Shelton Martis in 2009.
Newcastle new boys impress
Wijnaldum is the most expensive signing of Newcastle owner Mike Ashley's eight-year reign and the Netherlands international looked right at home at St James' Park, looking to get forward and providing a strong driving force from midfield.
He capped his display with a wonderful headed goal, rising to meet Gabriel Obertan's cross to power past keeper Maarten Stekelenburg.
Centre-back Chancel Mbemba, an £8.5m signing from Anderlecht, grew into the game after being out-jumped for Pelle's opener. The DR Congo international could soon become a favourite among Newcastle fans after arriving at the match dressed in a tuxedo.
It was almost a nightmare debut for Newcastle's other new signing, £13m Serbia striker Aleksandar Mitrovic, who was booked 22 seconds after coming on as a second-half substitute.
Man of the Match - Georginio Wijnaldum
Newcastle manager Steve McClaren: "I went through every emotion. We played some terrific football and could have been out of sight.
In the end we hung on for the point and there were a lot of positives. It would have been a travesty if we had lost.
"In the last 15 minutes we have to be smarter, we will learn from that."
On Mitrovic's booking: "We were quite fortunate he did not get a red there and there would have been no complaints if he did. That's what he is. He certainly doesn't hold back. He wanted to come on and impress."
Southampton assistant manager Erwin Koeman: "We had some big chances in the last 10 minutes but you have to score to win games so it is mixed feelings that we have.
"It is not a bad start, but if you are professional and you get the chance to win, you have to win.
"Ten minutes before the end I thought OK, we are happy with a point, but if you see the last 10 minutes then we have to be disappointed."
Former Scotland winger Pat Nevin on BBC Radio 5 live: "Steve McClaren will have learned a lot about his team today. For 75 minutes they were the better side but he made a few changes and he needs to work out why they did not work. But those 75 minutes were better than anything else I saw from Newcastle last season. He has something to build on here."
The stats you need to know
- Newcastle ended a run of three straight defeats by Southampton.
- Pelle scored only his second Premier League goal away from St Mary's for Southampton. He has scored 13 in total.
- The Magpies have managed only one clean sheet in their last 17 top-flight clashes against Southampton.
- Southampton have conceded exactly two goals in each of their last five away games.
- 8AnitaSubstituted forTiotéat 68'minutes
- 4ColbackBooked at 55mins
- 5WijnaldumSubstituted forde Jongat 81'minutes
- 9CisséSubstituted forMitrovicat 75'minutesBooked at 75mins
- 10de Jong
- 2Cédric SoaresBooked at 12minsSubstituted forMartinaat 45'minutes
- 6José FonteBooked at 60mins
- 8DavisBooked at 87mins
- 9RodriguezSubstituted forLongat 65'minutes
- 19PellèBooked at 90mins
- Craig Pawson
- Shots on Target
Second Half ends, Newcastle United 2, Southampton 2.
Attempt missed. Sadio Mané (Southampton) left footed shot from the centre of the box is close, but misses to the left. Assisted by Dusan Tadic.
Graziano Pellè (Southampton) is shown the yellow card for a bad foul.
Cheick Tioté (Newcastle United) wins a free kick in the defensive half.
Foul by Graziano Pellè (Southampton).
Foul by Aleksandar Mitrovic (Newcastle United).
Maya Yoshida (Southampton) wins a free kick in the defensive half.
Attempt blocked. Sadio Mané (Southampton) right footed shot from the centre of the box is blocked. Assisted by Steven Davis.
Corner, Southampton. Conceded by Chancel Mbemba.
Steven Davis (Southampton) is shown the yellow card for a bad foul.
Massadio Haidara (Newcastle United) wins a free kick in the defensive half.
Foul by Steven Davis (Southampton).
Attempt missed. Shane Long (Southampton) right footed shot from outside the box is high and wide to the right. Assisted by Dusan Tadic.
Substitution, Newcastle United. Siem de Jong replaces Georginio Wijnaldum.
Goal! Newcastle United 2, Southampton 2. Shane Long (Southampton) header from the centre of the box to the top left corner. Assisted by Dusan Tadic with a cross.
Aleksandar Mitrovic (Newcastle United) is shown the yellow card for a bad foul.
Foul by Aleksandar Mitrovic (Newcastle United).
Matt Targett (Southampton) wins a free kick in the defensive half.
Substitution, Newcastle United. Aleksandar Mitrovic replaces Papiss Demba Cissé.