The slashing of around one in five of its workforce, to 74,000 employees, is an unprecedented round of departures for Deutsche.
The bank said the layoffs would reduce annual costs by €6 billion euros over the same period.
“Today we have announced the most fundamental transformation of Deutsche Bank in decades,” chief executive Christian Sewing said, dubbing the scheme “a restart for Deutsche Bank”.
The lender did not immediately make clear where the axe would fall.
But with executives looking to find synergies in the integration of subsidiary Postbank and central infrastructure roles, many jobs are likely to go in home country Germany.
The new round of job cuts comes on top of some 6,000 already carried out over the past year.
Bosses expect the restructuring plan to sap second-quarter results by some three billion euros this year, making for a net loss of 2.8 billion.
Over the whole year, Deutsche is likely to plunge back into the red after a brief flirtation with profitability in 2018.
The bank does not plan to pay out dividends this year or next.
The restructuring could be a last chance for Deutsche after much-hyped merger talks with crosstown rival Commerzbank fell through earlier this year.
Negotiations collapsed despite the backing of the finance ministry in Berlin, which feared seeing a vital link in the financing of the country's economy bought up from abroad.
Over the past four years, the firm's market capitalization has fallen by 75 percent, making it a potential target for takeovers by bigger fish.
As markets closed Friday, Deutsche was worth €15 billion, placing it firmly at the back of the pack in a European industry dominated by the likes of HSBC (€165 billion euros), Spain's Banco Santander (€69 billion) and France's BNP Paribas (€54 billion).
“Deutsche plays in the first division, and should lay the foundations for things to stay that way” over the weekend, urged economy minister Peter Altmaier in the tabloid-style Bild's Sunday edition.
Since he took the helm in early 2018, Sewing has attempted to refocus the sprawling group on stable revenue-generating business areas, including retail banking and so-called transaction banking for businesses.
Meanwhile Deutsche's focus has shifted from its attempt to compete with US-based global giants back to its home turf of Germany and Europe.
Investment banking burned
In particular, tough cuts to the former flagship investment banking unit have been on the agenda since May.
Sunday's announcements target the once-proud division.
Deutsche will stop almost all share trading activity, and is in talks with France's BNP Paribas to sell off some of its business and staff in the field.
On Friday, Garth Ritchie, the head of Deutsche's South African investment banking unit, was first out of the door.
The unit's business had fallen back by 20 percent in the first quarter of 2018 alone, and it was no longer bringing in the fat profits of former years.
Especially in the US, it was for years plagued by lawsuits and scandals, including some linked to the so-called “Panama Papers” leak of sensitive documents about offshore dealings.
On top of the rank-and-file cuts, Deutsche is also rebuilding its board, sending away compliance chief Sylvie Matherat and two other executives.
The group will also create a so-called “bad bank” unit to host some €74 billion of low-quality assets, notably those linked to derivatives transactions — highly speculative financial products.
Deutsche's woes are a microcosm of a struggling German banking sector that was once widely envied.
Last year, more than 32,000 jobs were cut in the industry, or 5.4 percent of the total workforce of 565,000, according to Barkow Consulting figures.
Bosses complain that low interest rates in the eurozone, sluggish economic growth and competition from new online platforms are sapping their performance.