Sir Andrew Witty will retire on 31 March 2017, ending more than three decades at the pharmaceuticals giant and sparking the hunt for his successor.
In the company's annual report published separately, it was also revealed that Sir Andrew was awarded a total pay package worth £6.7mlast year - up 71% on the £3.9m paid out for 2014 - despite falling core earnings and sales in 2015.
He was paid a salary of just under £1.1m for 2015, while he was also handed an annual bonus payment of £2.2m and long-term share awards worth £2.6m, although 25% of his annual bonus is deferred.
GlaxoSmithKline revealed in its annual results in February that core operating profit fell last year by 13% to £5.73bn when rising vaccine and consumer healthcare sales failed to offset falls at its key pharmaceuticals unit.
However, the fall in annual core operating profit was tempered by a 2% rise in fourth- quarter sales to £6.29bn, beating analyst expectations.
On his decision to retire, Sir Andrew said: "In making this decision it has been important to me that the board have the time to conduct a full and proper process and that we sustain the momentum of our current business performance, capitalising on the very significant progress we made last year to strengthen the group."
But the announcement comes as the FTSE 100 firm faces shareholder pressure to overhaul the business by splitting it into four different companies.
Fund manager Neil Woodford called for Glaxo to be broken up in January.
Sir Andrew joined Glaxo in 1985 and rose through the ranks after working in sales and marketing roles for the company's respiratory, HIV and infectious diseases fields.
He was appointed chief executive in May 2008 and received a knighthood for his services to the economy and the UK pharmaceutical industry in 2012.
But he suffered a blot on his copybook after the firm was also found guilty of bribery by the Chinese government and hit with a £297m fine in September 2014, following allegations that the drugs giant paid bribes to doctors and hospitals so they would promote its products.
And in February this year, Glaxo and a number of generic pharmaceuticals firms were fined £45m by Britain's Competition and Markets Authority (CMA) for anti-competitive practices.
The CMA said Glaxo made more than £50m of payments to companies making cheaper generic versions of its anti-depressant Seroxat to delay them coming to market.
Glaxo's shares were down more than 1% after news of Sir Andrew's departure plans.
The announcement also came as fellow FTSE 100 firm Rio Tinto said chief executive Sam Walsh will retire from the mining giant on 1 July this year and will be succeeded by Copper & Coal chief executive Jean-Sebastien Jacques.