Acknowledgements: We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; ANID, Chile; CAS, MOST and NSFC, China; Minciencias, Colombia; MEYS CR, Czech Republic; DNRF and DNSRC, Denmark; IN2P3-CNRS and CEA-DRF/IRFU, France; SRNSFG, Georgia; BMBF, HGF and MPG, Germany; GSRI, Greece; RGC and Hong Kong SAR, China; ISF and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; NWO, Netherlands; RCN, Norway; MEiN, Poland; FCT, Portugal; MNE/IFA, Romania; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZŠ, Slovenia; DSI/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TENMAK, Türkiye; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, CANARIE, Compute Canada and CRC, Canada; PRIMUS 21/SCI/017 and UNCE SCI/013, Czech Republic; COST, ERC, ERDF, Horizon 2020 and Marie Skłodowska-Curie Actions, European Union; Investissements d’Avenir Labex, Investissements d’Avenir Idex and ANR, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF, Greece; BSF-NSF and MINERVA, Israel; Norwegian Financial Mechanism 2014-2021, Norway; NCN and NAWA, Poland; La Caixa Banking Foundation, CERCA Programme Generalitat de Catalunya and PROMETEO and GenT Programmes Generalitat Valenciana, Spain; Göran Gustafssons Stiftelse, Sweden; The Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN, the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA), the Tier-2 facilities worldwide and large non-WLCG resource providers. Major contributors of computing resources are listed in Ref. [118].AbstractThis paper presents the observation of four-top-quark (ttˉttˉ
t
t
¯
t
t
¯
) production in proton-proton collisions at the LHC. The analysis is performed using an integrated luminosity of 140 fb−1
fb
-
1
at a centre-of-mass energy of 13 TeV collected using the ATLAS detector. Events containing two leptons with the same electric charge or at least three leptons (electrons or muons) are selected. Event kinematics are used to separate signal from background through a multivariate discriminant, and dedicated control regions are used to constrain the dominant backgrounds. The observed (expected) significance of the measured ttˉttˉ
t
t
¯
t
t
¯
signal with respect to the standard model (SM) background-only hypothesis is 6.1 (4.3) standard deviations. The ttˉttˉ
t
t
¯
t
t
¯
production cross section is measured to be 22.5−5.5+6.6
22
.
5
-
5.5
+
6.6
fb, consistent with the SM prediction of 12.0±2.4
12.0
±
2.4
fb within 1.8 standard deviations. Data are also used to set limits on the three-top-quark production cross section, being an irreducible background not measured previously, and to constrain the top-Higgs Yukawa coupling and effective field theory operator coefficients that affect ttˉttˉ
t
t
¯
t
t
¯
production.</jats:p